title: Curcumin analogue T83 exhibits potent antitumor activity and induces radiosensitivity through inactivation of Jab1 in nasopharyngeal carcinoma.
abstract: BACKGROUND
  Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus-associated malignancy that is most common in East Asia, Africa, and Alaska. Radiotherapy is the main treatment option; unfortunately, disease response to concurrent radiotherapy and chemotherapy varies among patients with NPC, and in many cases, NPC becomes resistant to radiotherapy. Our previous studies indicated that Jab1/CSN5 was overexpressed and plays a role in the pathogenesis and radiotherapy resistance in NPC. Therefore, it is important to seek for innovative therapeutics targeting Jab1/CSN5 for NPC. In this study, we explored the antitumor effect of a curcumin analogue T83 in NPC, and found T83 exhibits antitumor activity and induces radiosensitivity through inactivation of Jab1 in NPC.
  
  
  METHODS
  NPC cell viability and proliferation were detected by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation assays. Cell cycle distribution was detected with use of flow cytometry. Apoptosis was examined by using the Annexin V/propidium iodide staining assay and cleavage poly(ADP-ribose polymerase (PARP) and cleavage caspase-3 expression. Jab1 expression was examined by Western blotting.
  
  
  RESULTS
  A growth inhibitory effect was observed with T83 treatment in a dose- and time-dependent manner. T83 significantly induced G2/M arrest and apoptosis in NPC. In addition, T83 inhibited Jab1 expression and sensitized NPC cells to radiotherapy.
  
  
  CONCLUSIONS
  Our data indicate that T83 exhibits potent inhibitory activity in NPC cells and induces radiotherapy sensitivity. Thus, T83 has translational potential as a chemopreventive or therapeutic agent for NPC.
authors.affiliation: Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong 510080, People's Republic of China.
authors.forename: Yunbao
authors.initials: Y
authors.lastname: Pan
authors.forename: Mengyao
authors.initials: M
authors.lastname: Wang
authors.forename: Xianzhang
authors.initials: X
authors.lastname: Bu
authors.forename: Yinglin
authors.initials: Y
authors.lastname: Zuo
authors.forename: Sumei
authors.initials: S
authors.lastname: Wang
authors.forename: Dujuan
authors.initials: D
authors.lastname: Wang
authors.forename: Qing
authors.initials: Q
authors.lastname: Liu
authors.forename: Bojin
authors.initials: B
authors.lastname: Su
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.forename: Chunhua
authors.initials: C
authors.lastname: Wang
authors.forename: Francois X
authors.initials: FX
authors.lastname: Claret
authors.forename: Huiling
authors.initials: H
authors.lastname: Yang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D000075686:COP9 Signalosome Complex; D002277:Carcinoma; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism*; D034741:RNA, Small Interfering; D011836:Radiation Tolerance / Q000187:drug effects; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014162:Transfection
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D034741:RNA, Small Interfering; D011838:Radiation-Sensitizing Agents; C584430:T83 compound; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; D000075686:COP9 Signalosome Complex; D003474:Curcumin